N,N-Diethylaniline → Methyl 4-hydroxy-3-(1-vinylcyclopentyl)benzoate

Temperature

240 °C

A mixture of methyl 4-(2-cyclopentylideneethoxy)benzoate 66.67B (0.50 g, 2.0 mmol), N,N-diethylaniline (3.2 mL, 20 mmol) and N,O-bis(trimethylsilyl)acetamide (2.5 mL, 10 mmol) in a 20 mL seal tube was heated at 240° C. for 48 hours. The reaction was then cooled to room temperature, ether (60 mL) was added, and the mixture was washed with HCl (3N, 20 mL). The organic layer was separated and the solvent was removed. The residue was dissolved in MeOH (10 mL) and HCl (3N, 2 mL) and stirred at room temperature for 30 minutes. Ether (80 mL) was added, and the mixture was washed with NaHCO3 (30 mL) and brine (15 mL). The organic layer was dried over MgSO4. After filtering, the solvent was removed. The residue was purified by Combi Flash silica gel column, eluting with hexane/EtOAc (95/5) to give the compound 66.67C, (0.15 g, yield 30%). 1H NMR (500 MHz, CDCl3) δ ppm 7.90 (1H, d, J=2.2 Hz), 7.80 (1H, dd, J=8.3, 2.0 Hz), 6.81 (1H, d, J=8.3 Hz), 5.99 (1H, dd, J=17.6, 10.5 Hz), 5.77 (1H, s), 5.18 (1H, dd, J=10.5, 1.0 Hz), 5.08 (1H, d, J=17.6 Hz), 3.82 (3H, s), 1.89-2.03 (4H, m), 1.56-1.78 (4H, m). MS ESI (neg.) m/e: 245.1 (M−H)+.

1. customseal tube
2. temperatureThe reaction was then cooled to room temperature
3. washthe mixture was washed with HCl (3N, 20 mL)
4. customThe organic layer was separated
5. customthe solvent was removed
6. dissolutionThe residue was dissolved in MeOH (10 mL)
7. additionEther (80 mL) was added
8. washthe mixture was washed with NaHCO3 (30 mL) and brine (15 mL)
9. dry with materialThe organic layer was dried over MgSO4
10. filtrationAfter filtering
11. customthe solvent was removed
12. customThe residue was purified by Combi Flash silica gel column
13. washeluting with hexane/EtOAc (95/5)

ORD record

ord-4fd529074b8f4bd288eb4b50cd770a5f

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030354B2